Melanocortins, products of pro-opiomelanocortin (POMC) post-translational processing, are known to have a broad array of physiological actions. Nakanishi, S. et al., Nature 278:423-427 (1979). Aside from their well known effects on adrenal cortical functions (adrenocorticotropic hormone, ACTH) and on melanocytes (melanocyte stimulating hormone, MSH), melanocortins have been shown to affect behavior, learning, memory, control of the cardiovascular system, analgesia, thermoregulation, and the release of other neurohumoral agents including prolactin, luteinizing hormone, and biogenic amines. De Wied, D. et al., Methods Achiev. Exp. Pathol. 15:167-199 (1991 ); De Wied, D. et al., Physiol. Rev. 62:977-1059 (1982); Gruber, K. A. et al., Am. J. Physiol. 257:R681-R694 (1989); Murphy, M. T. et al., Science 210:1247-1249 (1980); Murphy, M. T. et al., Science 221:192-193 (1983); Ellerkmann, E. et al., Endocrinol. 130:133-138 (1992) and Versteeg, D. H. G. et al., Life Sci. 38:835-840 (1986). Peripherally, melanocortins have been identified to have immunomodulatory and neurotrophic properties, and to be involved in events surrounding parturition. Cannon, J. G. et al., J. Immunol. 137:2232-2236 (1986); Gispen, W. H., Trends Pharm. Sci. 11:221-222 (1992); Wilson, J. F., Clin. Endocrinol. 17:233-242 (1982); Clark, D. et al., Nature 273:163-164 (1978) and Silman, R. E. et al., Nature 260:716-718 (1976). Furthermore, melanocortins are present in a myriad of normal human tissues including the brain, adrenal, skin, testis, spleen, kidney, ovary, lung, thyroid, liver, colon, small intestine and pancreas. Tatro, J. B. et al., Endocrinol. 121:1900-1907 (1987); Mountjoy, K. G. et al., Science 257:1248-1251 (1992); Chhajlani, V. et al., FEBS Lett. 309:417-420 ( 1992); Gantz, I. et al. (accepted for publication, J. Biol. Chem., 1993) and Gantz, I. et al. (submitted for publication, 1993).
Recent studies have described an unexpected diversity of subtypes of receptors for the melanocodin peptides and determined that they all belong to the superfamily of seven transmembrane G-protein linked cell surface receptors. Mountjoy, K. G. et al., Science 257:1248-1251 (1992); Chhajlani, V. et al., FEBS Lett. 3:417-420 (1992); Gantz, I., J. Biol. Chem. 268:8246-8250 (1993) and Gantz, I. et al., J. Biol. Chem.(in press 1993). Although no ligand binding experiments were described, Mountjoy, K. G. et al., reported the gene sequences encoding the .alpha.-MSH receptor and the ACTH receptor. Science 257:1248-1251 (1992). Independently, Chhajlani, V. et al., reported a similar sequence for the .alpha.-MSH receptor and demonstrated specific binding of a stable MSH analogue to Cos-7 cells transfected with .alpha.-MSH receptor cDNA. FEBS Lett. 309:417-420 (1992). The .alpha.-MSH receptor has been identified as the melanocortin-1 receptor and the adrenocorticotropic hormone (ACTH) receptor as the melanocortin-2 receptor.
It would thus be desirable to isolate genes encoding melanocortin receptors. It would also be desirable to locate the chromosomal position of the melanocortin receptor genes. It would further be desirable to characterize melanocortin receptor binding and secondary signaling and determine tissue distribution of the melanocortin receptors. It would also be desirable to provide therapeutic vehicles for the treatment of processes involving the function of melanocortin receptors.